CN105566158B - A kind of preparation method of cyhalofop-butyl - Google Patents

Abstract

A kind of preparation method of cyhalofop-butyl, this method is first by (R) 2 (4 hydroxyphenoxy) propionic acid and 3, 4 difluorobenzonilyiles carry out etherification reaction and obtain (R) 2 [4 (2 fluorine, 4 itrile group) phenoxy group] propionic acid intermediate under alkaline condition, (R) 2 [4 (2 fluorine, 4 itrile group) phenoxy group] propionic acid intermediates obtain cyhalofop-butyl product with n-butanol through being esterified dehydration again, the preparation method of the present invention shortens reaction route, reduce production cost, avoid chloride step, equipment requirement is reduced, simplify operation, reduce three wastes discharge amount, there is huge directive significance to technique amplification and production.

Description

A kind of preparation method of cyhalofop-butyl

Technical field

The invention belongs to herbicide production fields, and in particular to a kind of preparation method of cyhalofop-butyl.

Background technology

Herbicide is to ensure the indispensable substance of agricultural production institute, and through measuring and calculating, if farmland not weeding, Crop damage will Reach 50~70%, in developed country, herbicide dosage accounts for the 40~50% of pesticide total amount, the use of China's herbicide in recent years Amount growth is also very fast, and more than have currently reached pesticide total amount 30%, and growth trend is very strong.

In recent years rice direct seeding field area constantly expands, and causes barnyard grass, moleplant seed radix to increase, crop smothering occurs serious.At present The larger herbicide of paddy field weed-killer dosage has butachlor, bensulfuron-methyl, dichloro quinolinic acid, this 3 kinds account for the market share 50% or more, and all used 20~30 years, the resistance of weeds is increasing year by year, and peasant has to the use for increasing pesticide control Amount.

Cyhalofop-butyl is a rice field post-emergence herbicide that weeds are presented with very high activity and selectivity in very low dose, It is mainly used for preventing and kill off important grassy weed, especially to barnyard grass (including above the average age for marriage barnyard grass), moleplant seed, amur foxtail, moderately well-off grass, horse Tang, Paspalum distichum, green bristlegrass, eleusine indica etc. have remarkable effect, very safe to rice class crop, and it has low toxicity, low residual The characteristics of staying.Moleplant seed harm is more serious in rice terrace, and the moleplant seed before the 4 leaf phase of cyhalofop-butyl pair shows high herbicide Activity, other medicaments can not be by comparison.

Cyhalofop-butyl is that uniquely have tight security to rice (transplanting and live streaming) in fragrant phenoxy phenoxy propionic acid herbicide Kind, there is excellent selectivity, excellent selectivity to be based on cyhalofop-butyl in rice body and weeds body rice etc. Interior to have different accretion rates, in rice body, it is inactive to acetyl-CoA carboxylase that cyhalofop-butyl, which can be degraded quickly, Two acid-state, thus rice is highly safe；And accretion rate of the cyhalofop-butyl in weeds body is slower, it can be effective Therefore the growth for inhibiting weeds, is pacified succession crop because cyhalofop-butyl is rapid with the degradation in typical rice field water in the soil Entirely.

Therefore, promoting and applying cyhalofop-butyl will play a significant role the increasing both production and income to national crops, and exploitation is efficient Herbicide cyhalofop-butyl will have good development prospect.

Cyhalofop-butyl, English common name：Cyhalofopbutyl, trade name：A thousand pieces of gold (clincher), chemical name： (R) -2- [4- (4- cyano -2- fluorophenoxies) phenoxy group] butyl propionate, English name：butyl(R)-2-[4-(4-cyano- 2-fluorophenoxy) phenoxy] propionate is the phenoxy carboxylic acid weeding of Dow agricultural sciences company exploitation Agent.Structural formula is：

Sterling is white crystalline body, 50 DEG C of fusing point, and vapour pressure is 1.2 × 10-6Pa (20 DEG C), and solubility is in water 0.7mg/L (20 DEG C, pH=7)；Stablize when pH=4, decompose when pH=7 slow, is decomposed rapidly when pH is 1~2 or 9.

Currently, the synthetic method use of cyhalofop-butyl is all chemical synthesis, principal synthetic routes have three：

Route 1：The fluoro- 4- of 3- (4- hydroxyphenoxies) cyanophenyl is obtained by the reaction in hydroquinone and 3,4- difluorobenzonilyiles, then and (S)-tolysulfonyl lactate reaction generates cyhalofop-butyl, and reaction equation is：

Although document report (《Pesticide》The 5th phase of volume 49 in 2010) route can obtain 97% or so (R)-isomers, But it is influenced by raw material and reaction condition, there are racemization phenomenons for reaction, are actually only capable of obtaining (R)-isomers of 80-90%, together When, from the aspect of cost, the route integrated artistic is longer, during 3,4- difluorobenzonilyiles are reacted with what biphenol occurred, to two Two phenolic hydroxyl groups of phenol each may participate in reaction, generate by-product, increase the dosage of 3,4- difluorobenzonilyiles, and 3,4- difluorobenzonilyiles It is expensive, therefore the route is expensive, also, the post-processing of p-methyl benzenesulfonic acid need to make in-depth processing of microbial degradation, Therefore this synthetic route is not generally industrially used.

Route 2：Using (S)-lactate as starting material, (S)-tolysulfonyl lactate, then same hydroquinone are first obtained (R) -2- (4- hydroxyphenoxies) propionic ester is obtained by the reaction, synthesis cyhalofop-butyl, reaction equation are then reacted with 3,4- difluorobenzonilyiles For：

《Pesticide research and application》The 1st phase of volume 11 in 2007 reports a kind of synthetic method of cyhalofop-butyl, and above-mentioned Route 2 is close, and synthetic route is：Using (S)-methyl lactate as raw material, (S)-tolysulfonyl methyl lactate is synthesized first, then Intermediate is obtained by the reaction with hydroquinone, then obtains (R) -2- (4- hydroxyphenoxies) third by hydrolysis, ethyl alcohol esterification Acetoacetic ester, then reacted with 3,4- difluorobenzonilyiles, (R) -2- [4- (4- cyano -2- fluorophenoxies) phenoxy group] ethyl propionate is obtained, It is hydrolyzed into acid again, acid generates cyhalofop-butyl with n-butanol by esterification again, however, this process route is long, it is cumbersome, together When, there is a large amount of waste water to generate, also, the p-methyl benzenesulfonic acid by-product generated can not recycle, it is difficult to handle.

Route 3：(R) -2- (4- hydroxyphenoxies) propionic acid and 3,4- difluorobenzonilyiles in organic solvent, base catalysis condition Lower progress condensation reaction generates intermediate (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid, intermediate again with phosgene into Row photochemical reaction generates intermediate (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionyl chloride, is finally carried out again with n-butanol Esterification generates cyhalofop-butyl, in this method, intermediate (R) -2- [4- (2- fluorine-4-nitriles)-benzene oxygen before being prepared into ester Base]-propionic acid when, carried out acyl chloride reaction, when chloride has used phosgene or thionyl chloride etc. toxic, deep-etching acid former Material, it is more demanding to experimental facilities and operation, increase security risk.

Invention content

The purpose of the present invention is to provide a kind of preparation methods of cyhalofop-butyl, shorten reaction route, reduce production Cost；Chloride step is avoided, equipment requirement is reduced, simplifies operation, reduces three wastes discharge amount, technique is amplified and raw Production has huge directive significance.

In order to achieve the above object, technical solution provided by the invention is as follows：

A kind of preparation method of cyhalofop-butyl, includes the following steps：

1) etherification reaction

Alkali is added into polar non-solute as acid binding agent, adds reaction substrate (R) -2- (4- hydroxyphenoxies) Propionic acid and 3,4- difluorobenzonilyiles, heat temperature raising, reaction temperature are 80~120 DEG C, react 5-15 hours, remove pole after reaction Property aprotic solvent, be dissolved in water, be adjusted with acid pH to 4~5, precipitate crystal, filter, obtain intermediate (R) -2- [4- (2- Fluorine-4-nitrile)-phenoxy group]-propionic acid；

2) esterification

Intermediate (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid that step 1) is obtained and n-butanol, dehydration Reaction vessel is added in solvent and bronsted acid catalyst, obtains reaction solution, is heated to reflux, divides water, until anhydrous separate, reaction knot Reaction solution after reaction is washed to neutrality by beam, and removing solvent obtains cyhalofop-butyl；

Wherein, the dehydrated solvent refer to boiling point less than 130 DEG C and water-immiscible arene, alkanes or Ketone non-proton organic solvent.

Preferably, the arene non-proton organic solvent in the dehydrated solvent is benzene,toluene,xylene or chlorine Benzene.

Preferably, the alkanes non-proton organic solvent is hexamethylene, n-hexane, normal heptane, 1,2-, bis- chloroethenes Alkane or chloroform.

Preferably, the ketone non-proton organic solvent is butanone or cyclopentanone.

Preferably, the polar non-solute in step 1) is selected from dimethyl sulfoxide, n,N dimethylformamide, N, N dimethyl At least one of acetamide and N-Methyl pyrrolidone.

Further, the acid binding agent in step 1) is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate and phosphorus At least one of sour potassium.

Further, mole of reaction substrate (R) -2- (4- hydroxyphenoxies) propionic acid, 3,4- difluorobenzonilyiles and acid binding agent Than being 1:1~1.5：2~5.

Preferably, the reaction temperature of step 1) is 80~100 DEG C, and the acid described in step 1) is selected from sulfuric acid, hydrochloric acid, nitre At least one of acid, phosphoric acid and oxalic acid.

Further, the reaction substrate described in step 1) (R) -2- (4- hydroxyphenoxies) propionic acid and 3,4- difluorobenzonilyiles Molar ratio be 1:1~1.5, n-butanol described in step 2) and intermediate (R) -2- [4- (2- fluorine-4-nitriles)-benzene oxygen Base]-propionic acid molar ratio be 1~2：1.

Further, the bronsted acid catalyst in step 2) is one or more in the concentrated sulfuric acid, p-methyl benzenesulfonic acid and phosphoric acid, The molar ratio of bronsted acid catalyst and (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid is 0.01~0.1：1.

First by (R) -2- (4- hydroxyphenoxies) propionic acid and 3 in the preparation method of the present invention, 4- difluorobenzonilyiles are in alkaline item Etherification reaction is carried out under part and obtains (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid intermediate, and [(2- is fluoro- by 4- by (R) -2- 4- itrile groups)-phenoxy group]-propionic acid intermediate again with n-butanol through be esterified dehydration obtain cyhalofop-butyl product, avoid acyl chlorides Change step, shorten reaction route, reduce cost, equipment requirement is reduced, simplifies operation, reduce three wastes discharge amount.

In the esterification reaction, toluene or benzene are to reaction raw materials (R) -2- [4- (fluoro- 4- nitriles of 2- for the preparation method of the present invention Base)-phenoxy group]-propionic acid dissolubility it is preferable, there are a large amount of n-butanols in reaction system, under acid catalysed conditions, reaction raw materials In carboxyl progress reacted at ester, the cyano in reaction raw materials may carry out alcoholysis reaction, generate by-product (R) -2- [4- (2- Fluoro- 4- butoxy carbonyls)-phenoxy group]-butyl propionate, which can be by recrystallizing removing.

The present invention advanced optimizes above-mentioned preparation method, can substantially reduce (the R) -2- of by-product in esterification [4- (the fluoro- 4- butoxy carbonyls of 2-)-phenoxy group]-butyl propionate content, by being used in the esterification reaction to (R) -2- [4- (2- Fluorine-4-nitrile)-phenoxy group]-poor the dehydrated solvent of propionic acid dissolubility, plays reduction (R) -2- in a manner of direct or indirect The effect of [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid solubility in a solvent, such as：When using hexamethylene as solvent, ring Hexane polarity is smaller, poor to the dissolubility of (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid；Using butanone as dehydration When solvent, butanone and water energy 1:4 is miscible, and according to principle of dynamics, water is liquid, and in butanone, the solution rate of water is more than admittedly The solution rate of (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid of phase, therefore, under the competition of water, in butanone (R) solubility of -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid substantially reduces, and greatly reduces reaction raw materials (R) -2- The dissolubility of [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid, therefore, when carrying out esterification, only a small amount of (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid dissolves in a solvent, and (R) -2- [4- (2- the fluorine-4-nitriles)-benzene dissolved on a small quantity Oxygroup]-propionic acid is mainly with n-butanol progress esterification, and with the progress of esterification, levels of n-butanol is reduced, is substantially reduced The probability of cyano butanol solution, to inhibiting by-product (R) -2- [4- (the fluoro- 4- butoxy carbonyls of 2-)-phenoxy group]-propionic acid fourth The generation of ester makes its content drop to 0.1% or less from 0.7% or so.

Compared with prior art, beneficial effects of the present invention are：

1) in the preparation method of cyhalofop-butyl of the invention, shorten reaction route, reduce purification operations, reduce at This, due to avoiding acyl chloride reaction, the requirement to equipment reduces, and further saves industrialization cost.

2) it when the present invention carries out esterification, can be used molten to (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid The poor dehydrated solvent of solution property, can effectively inhibit the progress of side reaction, reduce the generation of by-product, the content of major impurity is big It is big to reduce, make the content of by-product (R) -2- [4- (the fluoro- 4- butoxy carbonyls of 2-)-phenoxy group]-butyl propionate drop to 0.1% with Under, product quality is further improved, operating procedure is reduced, recrystallization is avoided to remove miscellaneous operation, is reduced because recrystallization process is made At product loss, improve esterification yield, reduce process costs.

Description of the drawings

Fig. 1 is the high-efficient liquid phase chromatogram spectrum of cyhalofop-butyl in the embodiment of the present invention 1.

Fig. 2 is the high-efficient liquid phase chromatogram spectrum of cyhalofop-butyl in the embodiment of the present invention 4.

Specific implementation mode

Below in conjunction with specific embodiment, the invention will be further described.

The preparation method of 1 cyhalofop-butyl of embodiment

1) etherification reaction

N,N-dimethylacetamide 100mL, potassium carbonate 60g (0.42mol) are put into 250ml four-hole boiling flasks, then in batches (R) -2- (4- hydroxyphenoxies) propionic acid 26g (0.14mol) is put into, after feeding intake, then puts into 3,4- difluorobenzonilyiles 20g (0.14mol) then heats to 120 DEG C, and insulation reaction 5 hours, reaction terminates.Solvent is evaporated off, is down to room temperature and adds Water 150mL dissolvings adjust pH value to 4~5 with 30% dilute sulfuric acid, and solid is precipitated in stirring, and (R) -2- [4- (fluoro- 4- of 2- are obtained by filtration Itrile group)-phenoxy group]-propionic acid is spare.

2) esterification

Put into 500ml four-hole boiling flasks above-mentioned intermediate (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid, 200mL benzene, n-butanol 18g (0.24mol) and concentrated sulfuric acid 1g, temperature rising reflux divide water, reaction to be separated to no moisture, and reaction terminates. It is three times 7 to pH by reaction solution washing, separates organic phase, evaporated under reduced pressure solvent obtains product, chemical content 95%, optical purity 98%, two-step reaction total recovery 89% (in terms of (R) -2- (4- hydroxyphenoxies) propionic acid), appearance is white solid, miscellaneous in product Matter (R) -2- [4- (the fluoro- 4- butoxy carbonyls of 2-)-phenoxy group]-butyl propionate is 0.76%, high performance liquid chromatography (HPLC) figure Spectrum is referring to Fig. 1, and content analysis is referring to table 1.

Table 1

Peak #	Retention time	Peak area	Peak height	Content %
					1	16.424	14745	2756	0.271
2	18.561	10618	1826	0.195
					3	22.920	5350858	898132	98.484
4	26.458	10070	1978	0.185
					5	26.745	5730	1195	0.105
6	26.983	41226	7662	0.759
					It is total		5433247	913550	100.000

As can be seen from Table 1, cyhalofop-butyl product HPLC contents are 98.48% (retention time 22.92min), in product Impurity (R) -2- [4- (the fluoro- 4- butoxy carbonyls of 2-)-phenoxy group]-butyl propionate is 0.76% (retention time 26.983min).

The preparation method of 2 cyhalofop-butyl of embodiment

1) etherification reaction

N,N-dimethylacetamide 100mL, potassium carbonate 80g (0.58mol) are put into 250ml four-hole boiling flasks, then in batches (R) -2- (4- hydroxyphenoxies) propionic acid 26g (0.14mol) is put into, after feeding intake, then puts into 3,4- difluorobenzonilyiles 25g (0.18mol) then heats to 100 DEG C, and insulation reaction 6 hours, reaction terminates.Solvent is evaporated off, is down to room temperature and adds Water 200mL dissolvings, with 20% salt acid for adjusting pH value to 4~5, stirring is precipitated solid, filters (R) -2- [4- (fluoro- 4- nitriles of 2- Base)-phenoxy group]-propionic acid is spare.

2) esterification

Put into 500ml four-hole boiling flasks above-mentioned intermediate (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid, 200mL toluene, n-butanol 15g (0.20mol) and concentrated sulfuric acid 1g, temperature rising reflux divide water to no moisture to separate, and reaction terminates.It will be anti- It is three times 7 to pH to answer liquid washing, separates organic phase, evaporated under reduced pressure solvent obtains product, chemical content 95.3%, optical purity 98%, two-step reaction total recovery 88% (in terms of (R) -2- (4- hydroxyphenoxies) propionic acid), appearance is white solid, miscellaneous in product Matter (R) -2- [4- (the fluoro- 4- butoxy carbonyls of 2-)-phenoxy group]-butyl propionate is 0.69%.

A kind of preparation method of 3 cyhalofop-butyl of embodiment, including：

1) etherification reaction

N,N-Dimethylformamide 100mL, potassium carbonate 40g (0.29mol) are put into 250ml four-hole boiling flasks, are thrown in batches Enter (R) -2- (4- hydroxyphenoxies) propionic acid 26g (0.14mol), after feeding intake, then puts into 3,4- difluorobenzonilyiles 20g (0.14mol) then heats to 105 DEG C, and insulation reaction 6 hours, reaction terminates.Solvent is evaporated off, is down to room temperature and adds Water 150mL dissolvings adjust pH value to 4~5 with 30% dilute sulfuric acid, and solid is precipitated in stirring, filters to obtain intermediate (R) -2- [4- (2- Fluorine-4-nitrile)-phenoxy group]-propionic acid is spare.

2) esterification

Put into 500ml four-hole boiling flasks above-mentioned intermediate (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid, 200mL butanone, n-butanol 18g (0.24mol) and p-methyl benzenesulfonic acid 0.5g, temperature rising reflux divide water, reaction to no moisture to separate, instead It should terminate.Reaction solution is washed twice with saturated sodium bicarbonate solution, washing is primary, separates organic phase, evaporated under reduced pressure solvent must produce Product, chemical content 97.1%, optical purity 99%, two-step reaction total recovery 91% is (with (R) -2- (4- hydroxyphenoxies) third Acid meter), appearance is white solid, and impurity (R) -2- [4- (the fluoro- 4- butoxy carbonyls of 2-)-phenoxy group]-butyl propionate is in product 0.05%.

Embodiment 4

1) etherification reaction

Dimethyl sulfoxide 150mL, sodium carbonate 75g (0.7mol) are put into 250ml four-hole boiling flasks, put into (R) -2- in batches (4- hydroxyphenoxies) propionic acid 26g (0.14mol), after feeding intake, then puts into 3,4- difluorobenzonilyiles 20g (0.14mol), then 90 DEG C are warming up to, insulation reaction 12 hours, reaction terminates.Solvent is evaporated off, is down to room temperature and water 200mL is added to dissolve, use 15% dust technology adjusts pH value to 4~5, and solid is precipitated in stirring, filters (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-the third Acid is spare.

2) esterification

Put into 500ml four-hole boiling flasks above-mentioned intermediate (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid, 150mL hexamethylenes, n-butanol 18g (0.24mol) and phosphoric acid 0.5g, temperature rising reflux divide water, reaction to no moisture to separate, reaction knot Beam.Reaction solution is washed to neutrality, separates organic phase, evaporated under reduced pressure solvent obtains product, chemical content 97.5%, optical purity 99%, two-step reaction total recovery 92.5% (in terms of (R) -2- (4- hydroxyphenoxies) propionic acid), appearance is white solid, in product Impurity (R) -2- [4- (the fluoro- 4- butoxy carbonyls of 2-)-phenoxy group]-butyl propionate is 0.02%, high performance liquid chromatography (HPLC) Collection of illustrative plates is referring to Fig. 2, and content analysis is referring to table 2.

Table 2

Peak #	Retention time	Peak area	Peak height	Content %
					1	15.588	32199	5714	0.320
2	19.346	9986992	1776978	99.184
					3	20.325	5999	1247	0.060
4	22.262	24528	5386	0.244
					5	22.509	17737	3701	0.176
6	22.754	1716	651	0.017
					It is total		10069171	1793587	100

As can be seen from Table 2, cyhalofop-butyl product HPLC contents are 99.18% (retention time 19.35min), in product Impurity (R) -2- [4- (the fluoro- 4- butoxy carbonyls of 2-)-phenoxy group]-butyl propionate is 0.017% (retention time 22.754min).

Embodiment 5

1) etherification reaction

N-Methyl pyrrolidone 160mL, potassium phosphate 108g (0.51mol) are put into 250ml four-hole boiling flasks, are put into batches (R) -2- (4- hydroxyphenoxies) propionic acid 26g (0.14mol), after feeding intake, then puts into 3,4- difluorobenzonilyiles 20g (0.14mol) then heats to 100 DEG C, and insulation reaction 7 hours, reaction terminates.Solvent is evaporated off, is down to room temperature and adds Water 200mL dissolvings adjust pH value to 4~5 with 20% dilute sulfuric acid, and solid is precipitated in stirring, filters (R) -2- [4- (fluoro- 4- nitriles of 2- Base)-phenoxy group]-propionic acid is spare.

2) esterification

Put into 500ml four-hole boiling flasks above-mentioned intermediate (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid, 150mL hexamethylenes, n-butanol 12g (0.16mol) and concentrated sulfuric acid 0.5g, temperature rising reflux divide water, reaction to no moisture to separate, react Terminate.Reaction solution is washed to neutrality, separates organic phase, evaporated under reduced pressure solvent obtains product, chemical content 97.3%, optical voidness Degree 99%, two-step reaction total recovery 92% (in terms of (R) -2- (4- hydroxyphenoxies) propionic acid), appearance are white solid, in product Impurity (R) -2- [4- (the fluoro- 4- butoxy carbonyls of 2-)-phenoxy group]-butyl propionate is 0.03%.

Embodiment 6

1) etherification reaction

N-Methyl pyrrolidone 100mL, cesium carbonate 80g (0.25mol) are put into 250ml four-hole boiling flasks, are put into batches (R) -2- (4- hydroxyphenoxies) propionic acid 26g (0.14mol), after feeding intake, then puts into 3,4- difluorobenzonilyiles 22g (0.16mol) then heats to 90 DEG C, and insulation reaction 7 hours, reaction terminates.Solvent is evaporated off, is down to room temperature and adds water 200mL dissolves, and adjusts pH value to 4~5 with 30% dilute sulfuric acid, solid is precipitated in stirring, filters (R) -2- [4- (fluoro- 4- nitriles of 2- Base)-phenoxy group]-propionic acid is spare.

2) esterification

Put into 500ml four-hole boiling flasks above-mentioned intermediate (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid, 200mL butanone, n-butanol 12g (0.16mol) and concentrated sulfuric acid 0.1g, temperature rising reflux divide water, reaction to no moisture to separate, reaction knot Beam.Reaction solution is washed to neutrality, separates organic phase, evaporated under reduced pressure solvent obtains product, chemical content 97.6%, optical purity 99%, two-step reaction total recovery 93% (in terms of (R) -2- (4- hydroxyphenoxies) propionic acid), appearance is white solid, miscellaneous in product Matter (R) -2- [4- (the fluoro- 4- butoxy carbonyls of 2-)-phenoxy group]-butyl propionate is 0.01%.

Claims (4)

1. a kind of preparation method of cyhalofop-butyl, which is characterized in that it includes the following steps：

1) etherification reaction

Alkali is added into polar non-solute as acid binding agent, adds reaction substrate (R) -2- (4- hydroxyphenoxies) propionic acid With 3,4- difluorobenzonilyiles, heat temperature raising, reaction temperature is 80~120 DEG C, reacts 5~15 hours, removes polarity after reaction Aprotic solvent is dissolved in water, and is adjusted with acid pH to 4~5, precipitates crystal, and filtering, obtaining intermediate (R) -2-, [(2- is fluoro- by 4- 4- itrile groups)-phenoxy group]-propionic acid；

Wherein, the polar non-solute is selected from dimethyl sulfoxide, n,N dimethylformamide, N, N dimethyl acetamide and N- first At least one of base pyrrolidones；It reaction substrate (R) -2- (4- hydroxyphenoxies) propionic acid, 3,4- difluorobenzonilyiles and ties up The molar ratio of sour agent is 1:1~1.5：2~5；The acid binding agent is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, carbon At least one of sour caesium and potassium phosphate；

2) esterification

Intermediate (R) -2- [4- (2- fluorine-4-nitriles)-the phenoxy group]-propionic acid and n-butanol, dehydrated solvent that step 1) is obtained And reaction vessel is added in bronsted acid catalyst, is heated to reflux, water is divided to be separated to anhydrous, reaction terminates, and obtains reaction solution, will be anti- Liquid is answered to be washed to neutrality, removing solvent obtains cyhalofop-butyl；

Wherein, the dehydrated solvent refers to that boiling point is less than 130 DEG C and water-immiscible arene, alkanes or ketone Non-proton organic solvent；The arene non-proton organic solvent is benzene,toluene,xylene or chlorobenzene；The alkane Class non-proton organic solvent is hexamethylene, n-hexane, normal heptane, 1,2- dichloroethanes or chloroform；The ketone aprotic Organic solvent is butanone or cyclopentanone.

2. the preparation method of cyhalofop-butyl according to claim 1, which is characterized in that the acid described in step 1) is selected from sulphur At least one of acid, hydrochloric acid, nitric acid, phosphoric acid and oxalic acid.

3. the preparation method of cyhalofop-butyl according to claim 1, which is characterized in that n-butanol described in step 2) with The molar ratio of intermediate (R) -2- [4- (2- fluorine-4-nitriles)-phenoxy group]-propionic acid is 1~2：1.

4. the preparation method of cyhalofop-butyl according to claim 1, which is characterized in that Protic Acid Catalyzed described in step 2) Agent is one or more in the concentrated sulfuric acid, p-methyl benzenesulfonic acid and phosphoric acid；[(2- is fluoro- by 4- with intermediate (R) -2- for bronsted acid catalyst 4- itrile groups)-phenoxy group]-propionic acid molar ratio be 0.01~0.1：1.